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Enhancing CHO by Mammalian Systems Biotechnology (eCHO systems)

Periodic Reporting for period 2 - eCHO Systems (Enhancing CHO by Mammalian Systems Biotechnology (eCHO systems))

Reporting period: 2017-01-01 to 2018-12-31

Chinese hamster (CHO) ovary cells are the production host for a +50 billion €/yr biopharmaceuticals market. Current CHO production platforms dates to 1980 and are based primarily on media and process optimisation with little consideration to the optimization of the cellular machinery. Fortunately, with the recent sequencing of the CHO genome, an opportunity has opened to significantly advance the CHO platform. The benefit will be advanced production flexibility and a lower production cost, which will potentially advance European biotechnology.
Specifically the objectives of eCHO Systems were:
a) To train PhDs to overcome the barriers that currently exist between systems and synthetic biology innovation and traditional mammalian biotechnology research and education paradigms.
b) To break barriers between industry and academia, such that PhD students gain expertise in the latest biotechnology methods used in the CHO industry, and provide practical experience to the students by working in both sectors. The students have also taken biotechnology business development courses to learn about entrepreneurship.
c) The PhDs have transfered state-of-the-art genome scale research approaches in systems biology, genome engineering, and computational/bioinformatics tools into CHO biotechnology companies. Conversely, industrial advisors have provided scientific and technical expertise on projects and a product-oriented focus that will apply eCHO Systems innovations to commercial processes.
In summary, the research objectives of eCHO Systems were to apply the new genomics and systems biology-based data on CHO cells for advancement of current research and per extension to impact the non-academic sector to generate added value and increased competitive edge for European biotechnology

At the conclusion of the network activities, we find that the Network has performed the planned actions and achieved the desired impact. We have completed all deliverables of the original project plan – with the exception of minor partial goals, that were abandoned due to the state of the art expanding even faster than expected – and achieved all desired milestones. According to the original objectives, we have trained 15 PhDs that have been exposed to a combination of traditional biotechnology and synthetic and systems biology. They have worked at the interface between industry and academia, and have functioned as bridge builders in both directions, increasing the value of the network through new and strengthened synergies. As many of the activities are still continuing and the ESRs are still contributing to more dissemination, the effect will even increase over the coming months.
The majority of the direct impact of the Network is in the training, dissemination and communication, and exploitation of the results. As such, these are addressed in details above. We further had two overarching goals to achieve in order to reach the desired impacts. As such, they succinctly describe what the program strives to achieve.
1) The next generation of CHO industrialists is trained from a systems perspective and at the same time receives the proper business training to understand the commercial biotechnology industry. It will in this context be important to understand the evolving regulatory climate that will allow greater flexibility in modifying manufacturing capabilities while ensuring product quality. This will be achieved by embedding these ESRs within the major biotechnology operators as proposed here and by providing them with intensive business and regulatory training in their specific graduate programs.
2) A sustained systems biology research and training paradigm is implemented that will allow academic and industrial users to continually enhance the capabilities of the CHO platform and bring it to a level comparable to microbial production platforms. This is achieved by implementing an updated multidisciplinary graduate program as described here to ensure that ESRs in this program and others around Europe are provided with the most advanced skills to enhance CHO technology in coming decades.

As for objective 1, this is where the socio-economic impact is most directly seen. We have put particular focus on making sure that all ESRs complete their business training courses and are exposed to both academic and industrial environments through secondments. At the same time, all ESRs were fully aware of all the projects and the other ESR´s theses within this network, both by attending the Annual Meetings and by keeping constant contact and discussion up via their social network activities. All of them thus have a comprehensive overview of the advantanges, disadvantages and possibilities that different systems biotechnology approaches offer and will be well able to implement these approaches in their future career.
For objective 2, we are fulfilling this by the numerous publications — most likely well above the target number — and the large datasets that were deposited into different repositories for scientific data. The ESRs in the program are indeed being trained according to these guidelines, and with the developing genome editing technologies, we are approaching what is possible in microbial platforms. Together these data and the tools developed will enable significant advances for the CHO platform technology.
In particular, the project has produced four major outputs:
1) General knowledge to improve the productivity, quality, and efficiency of CHO platform cell lines. This improves the economy of working with the CHO system in general.
2) new systems models for CHO cells. Such models allow researchers to plan new and efficient strategies as well as eliminate hypotheses before going into the lab.
3) new CHO cell line chassis generated through synthetic biology approaches. This opens up new product portfolio options with new options for revenue as well as reduces production costs long term, due to improved downstream properties.
4) a cadre of interdisciplinary graduates poised to transform biopharmaceutical biotechnology. Several of the original 15 ESRs are already seen by the European cell culture elite as the potential next generation of industry leaders.
All of these will help ensure the global competitiveness of the European biotechnology industry.
The eCHO Systems has produced four major outputs:
1) General knowledge to improve the productivity, quality, and efficiency of CHO platform cell lines
2) new systems models for CHO cells
3) new CHO cell line chassis generated through synthetic biology approaches
4) a cadre of interdisciplinary graduates poised to transform biopharmaceutical biotechnology.
All of these will impact the European biopharmaceutical industry.
We have established this in a high quality graduate-level training programme. Results have been communicated at multiple levels: high school students, scientific publications, presentations at research conferences and to biotechnology companies.
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